10. Liver Stage. Human infection is initiated when
sporozoites are injected with the saliva during
mosquito feeding. The sporozoites enter the
circulatory system and within 30-60 minutes will
invade a liver cell. Host cell entry, as in all
apicomplexa, is facilitated by the apical organelles.
After invading the hepatocyte, the parasite
undergoes an asexual replication. This replicative
stage is often called exoerythrocytic (or pre-
erythrocytic) schizogony.
11.
12. Blood Stage. Merozoites released from the infected liver
cells invade erythrocytes. The merozoites recognize
specific proteins on the surface of the erythrocyte and
actively invade the cells.
After entering the erythrocyte the parasite undergoes a
trophic period followed by an asexual replication. The
young trophozoite is often called a ring form due to its
morphology in Geimsa-stained blood smears. As the
parasite increases in size this 'ring' morphology disappears
and it is called a trophozoite. During the trophic period the
parasite ingests the host cell cytoplasm and breaks down
the hemoglobin into amino acids. A by-product of the
hemoglobin digestion is the malaria pigment, or hemozoin.
These golden-brown to black granules have been long
recognized as a distinctive feature of blood-stage parasites.
13. Nuclear division marks the end of the trophozoite
stage and the beginning of the schizont stage.
Erythrocytic schizogongy consists of 3-5 rounds
(depending on species) of nuclear replication
followed by a budding process. Late stage
schizonts in which the individual merozoites
become discernable are called segmenters. The
host erythrocyte ruptures and releases the
merozoites. These merozoites invade new
erythrocytes and initiate another round of
schizogony. The blood-stage parasites within a
host usually undergo a synchronous schizogony.
14. Sexual Stage. As an alternative to schizogony some
of the parasites will undergo a sexual cycle and
terminally differentiate into either micro- or
macrogametocytes. Gametocytes do not cause
pathology in the human host and will disappear
from the circulation if not taken up by a mosquito.
Gametogenesis, or the formation of micro- and
macrogametes, is induced when the gametocytes
are ingested by a mosquito. After ingestion by the
mosquito, the microgametocyte undergoes three
rounds of nuclear replication. The
macrogametocytes mature into macrogametes.
15.
16. Sporogony. After reaching the extracellular
space between the epithelial cells and the basal
lamina, the ookinete develops into an oocyst.
The oocysts undergo an asexual replication,
called sporogony, which culminates in the
production of several thousand sporozoites.
This generally takes 10-28 days depending on
species and temperature. Upon maturation the
oocyst ruptures and releases the sporozoites
which is stored in the salivary gland.
Cold stage – parasites are demonstrable in the blood during this stage.
Sample – collected before antimalarials are started.
Once negative, samples may be examined for atleast 3 consecutive days where clinical suspiciom of malaria persists
Problem with the kit – cannot distinguish between falciparum and mixed infection
Vivax is almost the only non falciparum malaria in India
DD IS BROAD AND INCLUDES VIRAL INFECTONS
WHO has identified 10 complications of falciparum malaria that defines severe malaria
Cerebral malaria - Develops after the patient has been ill for several days. Fatality rate iis 15-20%
Prostation = inability to sit/ stand/ eat without support in the absence of impaired comsciousness. Pathophysiology of this process is not well understood.
respiratory distress - poor prognostic factor…… rather than intrinsic lung pathology
Algid malaria – death occurs within hours.
TSS – due to impaired immune response to falciparum antigens.
Polymerization of toxic heme to hemozoin is prevented by foprmtatuon of CQ heme complex.
CQ- ALSO active against E. Histolytica, Giardia lamblia
Uses – nocturnal muscle cramps, varicose veins
Ex- chloroquine resistance
Sulfa doxine – pyrimethamine introduced following CQ resistance fell rapidly to resistane in the early 1980s
Mefloquine resistance occurred within 4-5 years after its introduction.
Chemical – malathion
Biological – larvivorous fish - guppy/ gambusia
Personal – screening of home with wire mesh, bed nets treatef with permethrine
Use of reellant cream DEET – Diethyl methyl benzmide
